Implementing a Stratified Vocational Advice Intervention for People on Sick Leave with Musculoskeletal Disorders: A Multimethod Process Evaluation

Journal of Occupational Rehabilitation - Purpose To perform a process evaluation of a stratified vocational advice intervention (SVAI), delivered by physiotherapists in primary care, for people on...     

Characterization study of the ryanodine receptor and of calsequestrin isoforms of mammalian skeletal muscles in relation to fibre types

Summary We have investigated high-affinity ryanodine-binding sites in membrane preparations from representative fast-twitch and slow-twitch muscles of the rabbit and rat, as well as from human mixed muscle. Our results, obtained in high-ionic strength binding buffer, demonstrate extensive similarities in binding affinity for [³H]ryanodine (Kd: about 10 nM) and a two-fold to four-fold difference in membrane density of the ryanodine receptor between fast-twitch and slow-twitch muscle of the rat and rabbit, respectively. The [³H]ryanodine-pCa relationship for the Ca²⁺-activation curve of ryanodine binding was found to be similar for all mammalian muscles, as tested at 20 nM ryanodine. With 10 mM caffeine or 50 M doxorubicin the pCa for half-maximal activation of [³H]ryanodine binding invariably shifted from an average pCa value of 6.5 to pCa 7.1–7.3. IC₅₀ values for the inhibition of [³H]ryanodine binding by Ruthenium Red, a Ca²⁺-release channel blocker, did not differ significantly (range 0.3–1.0 M). The Ca²⁺-dependence curve (range 1 nM–10 mM free Ca²⁺) that we have observed at 5 nM ryanodine, for [³H]ryanodine binding to terminal cisternae from rabbit fast-twitch, as well as slow-twitch muscle, is bell-shaped and differs from that obtained with cardiac terminal cisternae from the same species. Cardiac ryanodine receptor is also clearly distinguishable for electrophoretic mobility, Cleveland's peptide maps, and, most strikingly, for total lack of cross-reactivity with polyclonal antibody to fast skeletal RyR. By the same properties, the ryanodine receptor of fast- and slow-twitch muscle appear to be the same or a similar protein. On investigating the composition of calsequestrin in rat and human skeletal muscles, both in membrane-bound form and after purification by phenyl-Sepharose chromatography, we have been able to show that, independent of the animal species, the cardiac isoform, as characterized by the identical amino-terminal amino-acid sequence, pattern of immunoreactivity, and lack of Ca²⁺-dependent shift in mobility on SDS-PAGE, is exclusively expressed in slow-twitch fibres, together with the main fast-skeletal calsequestrin isoform. While our experimental findings strongly argue for the presence of only one population of skeletal-specific Ca²⁺-release channels in junctional terminal cisternae of mammalian fast-twitch and slow-twitch muscle, they at the same time suggest the existence of differences in calsequestrin modulation of Ca²⁺-release, depending on its isoform composition.     

Cross-cultural adaptation of the Norwegian version of the spinal stenosis measure

In order to satisfy the need of a tool for assessing the treatment of patients with degenerative lumbar spinal stenosis, an evaluation was made of the reliability, construct validity, and responsiveness of the Norwegian version of Spinal Stenosis Measure (SSM, original by Stucki)). This study was a part of a prospective, cohort study. About 75 patients referred for surgery for spinal stenosis participated in the study. A subsample of 30 patients answered the questionnaire twice, test and retest, with at least one week in between. The SSM was translated according to the Guillemin criteria. Reliability was assessed by Bland and Altman’s repeatability, intraclass correlation coefficient (ICC) and the coefficient of variance (CV). Internal consistency was assessed by Cronbach’s alpha. Construct validity was analysed by correlation analyses. Responsiveness was calculated by the effect size. The reliability between test and retest scores was good for all three subscales of SSM as the ICC-values were above 0.9 and the CVs were below 15%. Cronbach’s alpha was above 0.8. The correlation analyses showed high correlation between scales that assessed the same construct, and low to moderate correlation between scales that assessed different constructs. Large effect sizes were found in all the SSM subscales with effect sizes ≥1.2.The Norwegian SSM version has added a highly useful tool for assessing the disease specific status and outcome after treatment in patients who suffer from degenerative lumbar spinal stenosis.     

Fetal, neonatal and developmental outcomes of lithium-exposed pregnancies

Introduction

Many women with a bipolar disorder are of reproductive age and will need to continue lithium treatment during pregnancy. The teratogenic and perinatal effects of lithium are known, but not the long-term effects of lithium on neurodevelopment of the children. This study investigates growth, neurological, cognitive and behavioral development of children exposed to lithium in utero.

Method

In an observational retrospective cohort study 15 children who were exposed to lithium in utero were investigated at 3–15 years of age. Neurological development was tested using the Hempel or Touwen examination. Cognitive development was assessed with the Bayley Scales of Infant Development III, Wechsler Preschool and Primary Scale of Intelligence or the Wechsler Intelligence Scale for Children. Parents completed the Child Behavior Checklist to assess behavioral development and a standard questionnaire about general development of the child since birth.

Results

One child had signs of a minor neurological dysfunction, but without further clinical implications. The results of the cognitive tests were within normal limits, although most children had lower scores on the performance IQ subtest. Growth, behavior and general development were within the normal range.

Conclusions

Continuing lithium therapy during pregnancy did not cause adverse effects on growth, neurological, cognitive and behavioral development of exposed children.     

Characteristics of skeletal muscle calsequestrin: comparison of mammalian,amphibian and avian muscles

Summary Calsequestrin was identified in the isolated sarcoplasmic reticulum from skeletal muscle of three mammalian species (man, rat and rabbit) and from frog and chicken muscle, using electrophoretic and immunoblot techniques. It was further characterized in sarcoplasmic reticulum protein mixtures and at several stages of purification, following extraction with EDTA.We found extensive similarities in apparent molecular weight values, Stains All staining properties and in Cleveland's peptide maps, between mammalian calsequestrins, and no detectable difference within a species between fast and slow muscle. Human calsequestrin, with an apparent molecular weight of 60 000 when measured at alkaline pH and of 41 000 when measured at neutral pH, appears to be the smallest in size. Frog calsequestrin, although weakly cross-reactive with rabbit calsequestrin and having a relatively higher apparent molecular weight at alkaline pH (72 000), shares several significant properties with mammalian calsequestrins. It bound calcium with a high capacity (1300 nmol per mg protein), it contained about 32% acidic amino acid residues and focused at closely similar pI values. We observed the formation of a complex with Stains All absorbing maximally at 535 nm, rather than at 600 nm, and an even more marked shift in apparent molecular weight at neutral pH.We found distinct differences in the case of chicken calsequestrin, in addition to those previously reported. It is a highly acidic, calcium-precipitable protein, but its amino acid composition is contradistinguished by a higher ratio of glutamate to aspartate and its rate of electrophoretic mobility is minimally affected by changes in pH. It stained deep bluish with Stains All after gel electrophoresis and yielded a protein-dye complex in aqueous solution, absorbing maximally at 560 nm, and finally, it bound fluorescent Concanavalin A.